Functional brain imaging is based upon the assumption that localized changes in brain circulation(i.e., blood flow, blood volume, vascular mean transit time) and metabolism accurately reflect changes in neuronal activity. Positron emission tomography (PET) and magnetic resonance imaging (MRI) are able to measure changes in circulation and metabolism safely and accurately to provide a unique window into human brain function. However, our understanding of the relationship of brain circulation and metabolism to neuronal activity is incomplete as is our understanding of the respective roles of PET and MRI in investigating these issues. It is the purpose of this project to employ PET, MRI and magnetic resonance spectroscopy (MRS) together in normal human subjects as well as patients with selected diseases to obtain a more complete understanding of the basis for the signals obtained and the respective role to be played by PET and MRI in functional brain imaging. This project compliments work in the project by powers which explores in detail the relationship of brain function to the delivery, transport and metabolism of glucose. This project will also be important to the work in the project by Peterson where the role of MRI has yet to be determined. Finally, this project brings together the expertise and resources of 3 major research groups whose combined experience in functional brain imaging with PET (Raichle an Powers), MRI (Haacke and Lin) and MRS (Ackerman, Neil and Bretthorst) is unique and should ensure that significant new scientific information regarding human brain function will be forthcoming from the proposed studies.